(4-imidazolyl)piperidines, the preparation thereof and their application in therapy

Abstract

Compounds of general formula <IMAGE> I in which R1 denotes H, CH3 or C2H5, R denotes H or R2 and R2 denotes an alkyl, piperonyl, 3-(1-benzimidazolonyl)-propyl group; a group of formula <IMAGE> in which n is 0, 1, 2, or 3, X is a single bond or alternatively -O-, -S-, -NH-, -CO-, -CH=CH- or <IMAGE> and R3 is H, CH3, F, CN or an acyl group; or alternatively a group of formula <IMAGE> in which Z denotes an O or S atom or a divalent group NH, N -CH3 or N -CN, and R5 denotes an alkyl group, a cycloalkyl group which can bear a phenyl substituent, a phenyl group which can bear a CH3 or F substituent, a phenylalkyl(1-3 C) group or a naphthyl, adamantyl or p-toluenesulphonyl group. These compounds are useful to control the release of cerebral histamine and to increase the rate of renewal of cerebral histamine.

What is claimed is: 
     
       1. A compounds corresponding to the formula ##STR98## in which R 1  denotes a hydrogen atom or a methyl or ethyl group, R denotes a hydrogen atom or the radical R 2 , and   R 2  denotes a linear or branched alkyl group having 1 to 6 carbon atoms; a piperonyl group; a 3-(1-benzimidazolonyl)propyl group; a group of formula ##STR99##  in which n is 0, 1, 2 or 3, X is a single bond or alternatively --O--, --S--, --NH--, --CO--, --CH═CH-- or ##STR100##  and R 3  is H, CH 3 , halogen, CN, CF 3  or an acyl group --COR 4 , R 4  being a linear or branched alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms or a phenyl group which can bear a CH 3  or F substituent; or alternatively a group of formula ##STR101##  in which Z denotes an O or S atom or a divalent group NH, N--CH 3  or N--CN and R 5  denotes a linear or branched alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms which can bear a phenyl substituent, a cycloalkyl(3 to 6 C)alkyl(1 to 3 C, linear or branched) group, a phenyl group which can bear a CH 3 , halogen or CF 3  substituent, a phenylalkyl(1 to 3 C, linear or branched) group or a naphthyl, adamantyl or p-toluenesulphonyl group, as well as the pharmaceutically acceptable salts thereof.   
     
     
       2. A compounds according to claim 1, in which R 2  denotes a group of formula ##STR102## having the same meaning as in the formula I. 
     
     
       3. A compounds according to claim 2, in which Z is O or S or an NH group. 
     
     
       4. 4-(1-cyclohexylaminothiocarbonyl-4-piperidyl)-1H-imidazole. 
     
     
       5. 4-(1-cyclohexylaminocarbonyl-4-piperidyl)-1-cyclohexylaminocarbonyl-1H-imidazole. 
     
     
       6. 4-(1-cyclohexylaminocarbonyl-4-piperidyl)-1H-imidazole. 
     
     
       7. 4-[1-(4-cyclopropylcarbonylphenyl)-4-piperidyl]--H-imidazole. 
     
     
       8. 4-[1-(1-adamantylaminothiocarbonyl)-4-piperidyl]-1H-imidazole. 
     
     
       9. 4-[1-(m-fluorophenylaminocarbonyl)-4-piperidyl]-1H-imidazole. 
     
     
       10. 4-[1-(α-methylbenzylaminocarbonyl)-4-piperidyl]-1-(.alpha.-methylbenzylaminocarbonyl)-1H-imidazole. 
     
     
       11. Process for preparing a compounds according to claim 1, characterized in that 4-(4-imidazolyl)piperidine or one of its alkylated derivatives of formula ##STR103## in which R 1  has the same meaning as in the formula I, is reacted either with a halogenated derivative R' 2  X', R' 2  having the same meaning as R 2  except for the group of formula ##STR104##  and X' denoting a halogen, or, in this latter case, with a derivative of formula Z═C═N--R 5  in which Z and R 5  have the same meaning as in the formula I, and, where appropriate, partial decomposition is performed of the disubstituted derivative (I; R═R 2 ) thereby prepared, so as to obtain the corresponding monosubstituted derivative (I; R═H).   
     
     
       12. Pharmaceutical composition containing an amount effective to control the release of cerebral histimine and to increase the the rate of removal of cerebral histamine, a compound according to claim 1 and a therapeutically compatible excipient or vehicle.